Network Pharmacology Insights Into Statin‐Induced Coenzyme <scp>Q10</scp> Deficiency: Lipid Metabolic Crosstalk, <scp>TNF</scp> – <scp>MAPK</scp> Signaling, and Muscle Toxicity

This in silico network-pharmacology investigation delineates the molecular interplay linking statin-induced Coenzyme Q10 (CoQ10) deficiency to statin-associated muscle symptoms (SAMS). GeneCards-derived targets related to SAMS, CoQ10 deficiency, and statins were integrated, and the intersecting gene set was analyzed through STRING-based protein-protein interaction mapping, followed by hub-gene prioritization using CytoHubba. Functional enrichment via ShinyGO revealed that the 145 common genes converge predominantly on inflammatory, metabolic, and mitochondrial pathways. Tumor necrosis factor (TNF) emerged as a principal regulatory node, exerting influence through Mitogen-Activated Protein Kinase (MAPK)-mediated apoptotic and stress-response cascades that plausibly contribute to mitochondrial dysfunction, oxidative stress, impaired energy metabolism, and myocellular injury in the context of CoQ10 depletion. The constructed pathway-based interaction network illustrates how suppression of the mevalonate pathway by statins disrupts CoQ10 biosynthesis, sensitizing muscle tissue to cytokine-driven inflammatory signaling and amplifying apoptotic susceptibility. Collectively, the findings highlight the TNF-MAPK axis as a mechanistic core of SAMS pathophysiology and underscore the interconnected roles of immune activation, lipid metabolic imbalance, and mitochondrial impairment. These insights provide a molecular rationale for therapeutic strategies targeting mitochondrial preservation or inflammatory modulation, including CoQ10 supplementation, and reinforce the need for experimental and clinical validation to substantiate computationally derived predictions.